A263 IBS-D MICROBIOTA INDUCES GUT-BRAIN DYSFUNCTION BY DISRUPTING INTESTINAL NEURAL AND IMMUNE PATHWAYS
Bibliographic record
Abstract
Irritable Bowel Syndrome (IBS) is a disorder of the gut-brain axis, with altered gut function and frequent psychiatric co-morbidity. We have previously shown in gnotobiotic mice that fecal microbiota from patients with IBS with diarrhea (IBS-D) and co-morbid anxiety induces faster gastrointestinal transit, gut barrier dysfunction, immune activation and anxiety-like behavior. However, the exact mechanisms underlying these abnormalities are not understood. To investigate and characterize the role of neural and immune factors in the microbiota-mediated alteration of gut physiology and behaviour. The expression of 72 murine genes related to neural, immune, and epithelial function was measured with NanoString nCounter® gene assay on total RNA extracted from colonic sections of mice colonized with microbiota from IBS-D patients or healthy volunteers. Colonic histology sections were stained for F4/80+ cells and multi-parameter flow cytometry was used to survey population of conventional and innate-like lymphocytes from various lymphoid compartments including the spleen, mesenteric lymph nodes, lamina propria, and intra-epithelial lymphocytes. Mice colonized with IBS-D microbiota had a strong upregulation of neural genes involved in secretomotor function (VIP, ChAT, CALB), visceral sensitivity (NR2D and GABA-B), innate immunity (CD11c, CCR2, GATA-3, and GPR44) and regulation of epithelial integrity and control of commensal microbiota (Trefoil factor 3 and Lysozyme) compared to mice colonized with healthy microbiota. Lamina propria macrophages levels were higher in IBS-D colonized mice compared to healthy controls. Multi-parameter flow cytometry revealed similar frequencies of conventional T cells (CD3+CD4+ and CD3+CD8+) or B cells (CD19+B220+) in the spleen, MLN, and intestinal compartments between mice with IBS-D microbiota vs. healthy controls. However, there was a higher relative frequency of TCRαβ-TCRγδ -RORγt+ cells in the colonic lamina propria of mice with IBS-D microbiota compared to healthy controls. Our results demonstrate that the intestinal microbiota from patients with IBS-D and co-morbid anxiety alters multiple immune and neural system pathways involved in the regulation of gut function. IBS-D microbiota appears to affect the innate but not the adaptive immune system, with macrophages and innate lymphoid cells playing a key role. CIHROntario Graduate Scholarship (OGS) - Masters
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".